Serum Clozapine Levels and Dose-Exposure Relationships in Indian Patients: A Cross-Sectional Study.

INTRODUCTION

Asians probably need lower doses than Caucasians to reach therapeutic serum clozapine levels. However, heterogeneity within Asians is poorly explored in the literature. There is limited South Asian data to guide clinicians treating this population.

METHODS

We conducted a cross-sectional study to estimate serum clozapine concentrations in Indians on stable doses. We tested for significant associations using Pearson's correlation and Student's t-test. We calculated target therapeutic dose ranges across sex and smoking status using mean C/D (serum concentration-to-dose) ratios in these patient groups. As a preliminary analysis, we constructed a linear regression model of serum clozapine concentration using variables identified in bivariate analysis and exploratory regression analysis.

RESULTS

Eighty-two participants were included. The mean serum clozapine concentration was 703.57 ng/ml (SD = 355.31). The mean C/D ratio was 2.35 ng/ml/mg (SD = 1.11); it was 3.05 in female non-smokers, 1.39 in the single female smoker, 2.31 in male non-smokers, and 1.32 in male smokers. Calculated therapeutic doses ranged from a minimum of 115 mg in female non-smokers to a maximum of 455 mg in male smokers. Sex, smoking status, alcohol use, symptom severity, dose prescribed, and beedi smoking were significantly associated with clozapine pharmacokinetics. The regression model for serum concentrations (including sex, smoking status, and prescribed dose as variables) explained 38.5% of the variance.

CONCLUSIONS

South Asians have higher C/D ratios of clozapine compared to Caucasians and East Asians. They require lower doses to achieve therapeutic serum concentrations. Beedi smoking is associated with lower C/D ratios than cigarette smoking.